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Related Concept Videos

Types of Receptors: Cell Surface Receptors01:28

Types of Receptors: Cell Surface Receptors

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Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored (integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, converting an extracellular signal into an intracellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are...
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Internal Receptors01:31

Internal Receptors

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Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
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Enzyme-linked Receptors01:00

Enzyme-linked Receptors

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Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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G-protein Coupled Receptors01:21

G-protein Coupled Receptors

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G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
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Types of Receptors: Internal Receptors01:07

Types of Receptors: Internal Receptors

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Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
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Use of the Protease Fluorescent Detection Kit to Determine Protease Activity
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Programming T cells for Early Cancer Detection with Customized Protease-Activatable Receptors.

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    OncoSCOUT uses engineered T cells with protease-activatable receptors (PARs) for sensitive early cancer detection. This novel strategy detects small tumors by releasing a synthetic biomarker in urine, outperforming current methods.

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    Area of Science:

    • Biotechnology
    • Immunology
    • Oncology

    Background:

    • Early cancer detection significantly reduces mortality, but current biomarkers lack sensitivity for early-stage disease.
    • Endogenous tumor-shed biomarkers often fail to detect minimal residual disease or very small tumors.
    • Developing novel strategies for highly sensitive and specific cancer detection remains a critical unmet need.

    Purpose of the Study:

    • To develop and validate OncoSCOUT, a T cell-based cancer detection strategy utilizing protease-activatable receptors (PARs).
    • To engineer PARs that conditionally recognize tumor cells and release a detectable synthetic biomarker in urine.
    • To assess the sensitivity and specificity of OncoSCOUT for detecting small tumor burdens in vivo.

    Main Methods:

    • Engineered T cells expressing synthetic Notch receptors (PARs) with protease-cleavable linkers were designed.
    • A library of HER2-targeted PARs was screened in a HER2-positive cancer xenograft model.
    • OncoSCOUT's detection capability was evaluated against established biomarkers like CA 15-3 and circulating tumor DNA (ctDNA).

    Main Results:

    • OncoSCOUT demonstrated improved spatial specificity and reduced off-tumor activation by requiring both protease activity and tumor antigen recognition.
    • Multiple HER2-targeted PAR variants were identified and enriched in HER2-positive tumors.
    • OncoSCOUT detected tumor burdens as small as 10-30 mm³ with superior sensitivity compared to CA 15-3 and a 20-plex ctDNA assay.

    Conclusions:

    • OncoSCOUT represents a promising new strategy for early cancer detection, leveraging engineered T cells and synthetic biomarkers.
    • The system's ability to detect minute tumor volumes offers a significant advancement over current diagnostic methods.
    • Further development of OncoSCOUT could lead to improved patient outcomes through earlier intervention.